The mission of Human Brain Collection Core (HBCC) is to gain insight into the causes and mechanisms of mental disorders. To be able to conduct this research, we obtain brain tissues from deceased individuals with and without psychiatric disorders. The results will help us better understand brain dysfunction in mental disorders and develop new therapies and preventive strategies. We obtain brains through the Medical Examiners Offices (MEOs) of Northern and Central Virginia and the District of Columbia. Our personnel are notified of potential donations by MEOs and we contact the next-of-kin of the decedent to obtain consent for donation of the entire brain, blood samples, a small sample of scalp and hair. There is no cost to the next-of-kin or the decedent's family. There is also no direct benefit to the family for allowing the donation. The donation is strictly voluntary. We protect confidentiality of the decedent by removing his/her name and all identifying information from any materials we receive, and label all samples and the information derived from them only with a number. Our personnel audiotape the next-of-kin's consent as an official record of the donation, and make arrangements with the MEOs to collect the tissues. We try to obtain further information about the decedent's medical and psychiatric history through interviews with the family and released medical records, after obtaining written authorization from the next-of-kin. We will accept a donation even if the next-of-kin does not wish to answer follow-up questions. We do not provide any individual research results to the next-of-kin or the families or comments about the cause of death. The families are directed to contact the MEOs directly if they have further questions about the decedent. Our collection consists now of brain tissues from 1,003 subjects. From August 20, 2014, we collected 74 brains through the DC and Northern and Central VA Medical Examiners Offices. The breakdown by diagnosis for the tissues collected during this year is as follows: Anxiety disorder 1 Bipolar disorder 4 Non-psychiatric controls 4 Major Depressive Disorder 3 Neurological disorders 8 Schizophrenia 2 Substance abuse 2 Other 6 In the process of determining diagnosis 44 The major focus of our studies is elucidating the cellular and molecular pathophysiology of schizophrenia and mood disorders. Improved understanding of a genetic component in in mental illness may enhance diagnostic abilities and hopefully, lead to new treatments. Postmortem human brain studies are limited by the quality and quantity of the specimens. Through collaborations with NIH and extramural investigators, we have initiated the following molecular and genetic studies to address these questions: -Whole genome expression patterns in the dorsolateral prefrontal cortex, hippocampus and dura in several hundred individuals with mental disorders using microarray expression studies. -Gene expression patterns and associations with genetic variants using RNA and whole genome sequencing of dorsolateral prefrontal and anterior cingulate cortices in several hundred subjects with mental disorders and control individuals. -Cis regulatory epigenome mapping of the dorsolateral prefrontal and anterior cingulate cortices of subjects with schizophrenia and controls from the fluorescence-activated cell sorted (FACS) neuronal and non-neuronal populations using chromatin immunoprecipitation (ChIP) with massively parallel DNA sequencing (Chipseq). -Comprehensive identification of active gene regulatory elements in the dorsolateral prefrontal and anterior cingulate cortices of subjects with schizophrenia and controls from sorted (FACS) neuronal and non-neuronal cells using an Assay for Transposase-Accessible Chromatin with high throughput sequencing (ATAC-seq), a method for mapping chromatin accessibility genome-wide. -Alterations of miRNA expression in pyramidal and astrocyte cell populations in the dorsolateral prefrontal cortex (200 subjects, controls and schizophrenia) using Taqman assays. -Mapping bioactive lipids and RNA expression by RNA-sequencing in migraine headaches using trigeminal ganglia, blood, blood vessels and dura tissues. -Mapping gene expression by RNA-sequencing in the subgenual anterior cingulate cortex of subjects with depression who committed suicide and in bipolar disorder.